The tyrosine kinase inhibitor AG556 reduces serum tumor necrosis factor levels and tissue injury and improves survival in both small and large animal models of Gram-negative infection and sepsis. No data are presently available regarding the effects of AG556 during Gram-positive infection. We are therefore investigating this agent in rats challenged with Staphylococcus aureus. For these studies, we are using a multifactorial study design in which animals are challenged with low or high doses of S. aureus injected either intravenously or intrabronchially. This study design will allow us to determine how the site and severity of infection with S. aureus might alter the effects of AG556 on Gram-positive bacterial infection. This study has been started.